Abstract: TH-PO316
Kidney Function Differs Between 4.5-Month Virgin and 12-Month Breeder Female Sprague Dawley Rats
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Basic
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders
- 1001 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Basic
Authors
- Reilly, Timothy M., University of Southern California Keck School of Medicine, Los Angeles, California, United States
- Ralph, Donna, University of Southern California Keck School of Medicine, Los Angeles, California, United States
- McFarlin, Brandon E., University of Southern California Keck School of Medicine, Los Angeles, California, United States
- Edwards, Aurelie, Boston University, Boston, Massachusetts, United States
- McDonough, Alicia A., University of Southern California Keck School of Medicine, Los Angeles, California, United States
Background
Most studies of experimental hypertension and kidney disease are conducted in young virgin rodents, whereas human diseases are often associated with mid-life, suggesting that studies in older animals may offer translational advantages.
Methods
To assess age-based differences, we compared kidney function in virgin female (F) rats at 4.5 mo (240 gm), equivalent to 18-20 yr old humans, to 12 mo female breeders (320 gm), equivalent to 40 yr humans (n=6/group).
Results
Body, kidney and heart weights, as well as GFR (FITC sinistrin) were increased 30% between 4.5 and 12 mo. During 3 hr after a saline volume challenge, 4.5 mo F excreted twice the %Na and volume injected as 12 mo F. Responses to a 2% K meal were equivalent in 4.5 and 12 mo F. Baseline lithium clearance fell ~25% (P= 0.05) between 4.5 and 12 mo. Abundance of transporters, channels, and claudins varied along the nephron (Fig 1, *P< 0.05). SGLT1 (not SGLT2) and AQP2 phosphorylation increased 50% between 4.5 and 12 mo. Sodium pump (NKA) subunits were lower by ~ 50% in 12 mo vs 4.5 mo, paralleled by ~25% lower K-pNPPase activity in both cortex and medulla at 12 mo indicating changes in kidney energetics with age. NKCC2 and NCC phosphorylation decreased between 4.5 and 12 mo, however, diuretic tests with thiazides and furosemide were not depressed in parallel, perhaps reflecting impact of tubular flow and/or renal energetics.
Conclusion
Kidney function is significantly different in adult (12 mo) vs young (4.5 mo) F rats suggesting that middle aged rats may be more appropriate for (patho)physiology studies.
Funding
- NIDDK Support